Dressing Device for use with a Cannula or a Catheter

ABSTRACT

A method of protecting an insertion site permitting passage of a transcutaneous medical device into a patient. The method includes grasping a dressing device, positioning the dressing device over the insertion site, and adhering the dressing device to the patient over the insertion site. The dressing device may include a moisture vapor permeable backing, a polyurethane foam matrix, and an adhesive. The polyurethane foam matrix may be adhered to a first side of the moisture vapor permeable backing, and the adhesive may cover a second side of the moisture vapor permeable backing opposite of the first side. The polyurethane foam matrix can include a polyanhydroglucuronic acid or salt thereof in an amount to achieve a haemostatic effect, and chlorhexidine di-gluconate in an amount of 9% to 16% (w/w) to achieve an antimicrobial effect without adversely affecting wound healing.

PRIORITY

This is a division of U.S. patent application Ser. No. 13/808,183, filedJan. 3, 2013, which is a U.S. national stage application ofInternational Application No. PCT/IE11/00034, filed Jul. 4, 2011,claiming the benefit of priority to U.S. Provisional Application No.61/344,403, filed Jul. 14, 2010, each of which is hereby incorporated byreference in its entirety into this application.

INTRODUCTION

The present invention relates to a wound device, particularly for usewith IV catheters and other percutaneous devices.

Vascular and nonvascular percutaneous medical devices such as: IVcatheters, central venous lines, arterial catheters, dialysis catheters,peripherally inserted coronary catheters, mid-line catheters, drains,chest tubes, externally placed orthopedic pins, and epidural cathetertubes are widely used in modern day medical practice. Annually more than20 million inpatients in hospitals in the United States receiveintravenous therapy and almost 5 million require central venouscatheterization (Bouza et al., 2002)

Mechanical complications such as hemorrhage and thrombosis areassociated with catheterization. The risk of bleeding associated withcatheterization is reported to range between 1% and 8% (Mital et al.,2004) and although minor bleeding may be quite common serious bleedingis rare (Doerfler et al. 1996). Though dressings for antimicrobialeffectiveness have long been available no product deals sufficientlywith the bleeding from these wound types and this leads to dressingchanges being a regular occurrence. There remains a need for aneffective dressing for use with IV catheters that stops bleeding and isan effective antimicrobial solution.

Catheter use causes a semi-permanent breach of the skin that provides anaccess point for pathogens to enter the body, placing the patient atrisk for local and systemic infectious complications. The potential forinfection may be increased by proliferation of bacteria within orunderneath the dressing. Studies have shown that between 5% and 25% ofIV devices are colonized at the time of removal (Maki et al., 1998).Skin flora is the main source of microbial contamination and isresponsible for approximately 65% of catheter related infections.Bacteria from the skin migrate along the external surface of thecatheter and colonize the intravascular catheter tip leading to catheterrelated blood stream infections (Raad et al., 2001; Sheretz et al.,1997). Catheter-related bloodstream infection (CR-BSI) is the third mostcommon health care-acquired infection in the United States and isconsidered one of the most dangerous complications for patients. InEurope the incidence and density of central venous catheter (CVC)related bloodstream infections ranges from 1-3.1 per 1000 patient days(Suetens et al., 2007). Most organisms responsible for CR-BSIs originatefrom the insertion site of the catheter (Timsit, 2007), therefore,decreasing bacterial colonization at the site of insertion may helpreduce the incidence of CR-BSIs.

It is an object of the current invention to provide an improved wounddressing device that will provide protection at an insertion site.

SUMMARY OF THE INVENTION

According to the invention there is provided a dressing device for usewith a transcutaneous medical device such as a cannula or a catheter,the dressing device comprising a flexible hydrophillic polyurethanematrix, an antimicrobial agent contained within the matrix, and ahemostatic agent contained within the matrix, the hemostatic agentcomprising polyanhydroglucuronic acid or salt thereof in an amount toachieve a hemostatic effect, and the antimicrobial agent comprisingchlorhexidine di-gluconate in an amount to achieve an antimicrobialeffect without adversely affecting wound healing.

The invention provides a wound dressing device that prevents microbialcolonization of the dressing and stops bleeding from the insertion site.The device provides combined hemostatic and antimicrobial effects at theinsertion site but without adversely affecting wound healing.

This is a particularly surprising aspect of the invention because adressing composition that contains only polyanhydroglucuronic acid orsalt thereof to promote wound healing and hemostasis is not conducive tocontamination and infection control. The addition of chlorhexidinedi-gluconate as an antimicrobial agent effective at preventingcontamination and infection would be expected to adversely affect woundhealing. We have surprisingly found that this is not the case.

The polyanhydroglucuronic salt may be present in an amount of from 3% to20% (w/w). The polyanhydroglucuronic salt may for example be present inan amount of approximately 8% w/w.

The chlorhexidine di-gluconate may be present in an amount of from 9% to16% (w/w). The chlorhexidine di-gluconate may for example be present inan amount of approximately 11% w/w.

In one embodiment the dressing device comprises approximately 8% (w/w)polyanhydroglucuronic acid, approximately 11% (w/w) chlorhexidinedi-gluconate, and approximately 81% hydrophillic flexible polyurethanefoam.

In one embodiment the dressing device comprises an aperture forreception of a medical device such as a cannula or a catheter.

In one embodiment the dressing device comprises a breathable backingmaterial to allow vapor transmission from the device.

A skin contacting side of the device may contain an adhesive compound tokeep the device affixed to a site.

In one case the central access aperture is a circular hole ranging insize from 0.1 mm to 10 mm in diameter.

Alternatively the central access aperture is “x” shaped.

The central access aperture may be “T” shaped.

In one embodiment the device contains a quantity of the antimicrobialagent to maintain antimicrobial efficiency for up to 7 days.

The invention in one aspect is an absorbent polymeric wound dressingcontaining a broad spectrum antimicrobial agent and a hemostatic agentwith a moisture vapor permeable backing and radial slit and centralaccess hole to allow insertion of an IV catheter line or other similarpercutaneous device. The device contains sufficient quantities of thebroad spectrum antimicrobial agent to ensure that a clear antimicrobialzone of inhibition can be maintained around the insertion site and toprevent microbial contamination of the dressing. The device alsocontains sufficient quantities of hemostatic agent in order tosuccessfully control minor bleeding at the insertion site.

The absorbent polymer foam matrix dressing of the invention rapidlyaddresses bleeding, prevents dermal wound site contamination andinfection while at the same time promoting wound healing. Rapid woundhealing and closure in a controlled aseptic (near microbe free)environment provides the optimal conditions for reduced wound sitemorbidity.

The absorbent polymer foam matrix dressing composition of the inventionaddresses the paradoxical requirement of good antimicrobial efficacy,good hemostatic efficacy and good wound healing properties in the sameabsorbent, conformable polymer foam composition containing specificnarrow range non-antagonistic concentrations of antimicrobial,hemostatic and wound healing agents that allow for combined effectiveinteractions that are antimicrobial, hemostatic and wound healing.

A specific application of the present invention relates to a wounddevice, particularly for use with IV catheters and other percutaneousdevices.

The invention disclosure described herein identifies a novel devicecomposition which allows for the singular important advantage in beingable to attain antimicrobial, hemostatic and wound-healing promotingcharacteristics in a single absorbent and compliant device system.Normally achieving such functional heterogeneity in one device is notpossible due to antagonistic effects of the separate functions on oneanother. The unique feature of this invention is that it is able toidentify and integrate effective ranges for each active componentwithout adversely affecting the functions of the other components.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more clearly understood from the followingdescription of an embodiment thereof, given by way of example only, withreference to the accompanying drawings, in which:

FIG. 1 shows the results of the antimicrobial testing againstmethicillin-resistant Staphylococcus aureus (MRSA) using AATCC TestMethod 100-2004 after 24 hours incubation of sterilized polyurethanefoam matrix dressings containing polyanhydroglucuronic acid calciumsodium salt (8% w/w) dressing with increasing weight percent ofchlorhexidine di-gluconate (CHG) in a 217 mg, 25 mm diameter dressing;

FIG. 2 shows results of Kirby Bauer antimicrobial zone of inhibitiontesting after 24 hours incubation for the polyurethane foam matrixdescribed in example 3 and a commercially available chlorhexidinedi-gluconate containing matrix control material (intended to reducecatheter related blood stream infection) against methicillin resistantStaphylococcus aureus (MRSA), methicillin resistant Staphylococcusepidermidis (MRSE), Pseudomonas aeruginosa, vancomycin resistantEnterococcus faecium (VRE), Acinetobacter baumannii, Klebsiellapneumoniae and Candida albicans;

FIGS. 3A-3B show results of Kirby Bauer antimicrobial zone of inhibitiontesting after 1, 2, 3, 4, 5, 6 & 7 days for the polyurethane foam matrixdescribed in example 3 against the gram positive organisms (FIG. 3A)methicillin resistant Staphylococcus aureus (MRSA), methicillinresistant Staphylococcus epidermidis (MRSE), vancomycin resistantEnterococcus faecium (VRE) and the fungus and Candida albicans, andagainst gram negative organisms (FIG. 3B) Escherichia coli, Pseudomonasaeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae;

FIG. 4 shows the results of testing of suppression of re-growth of humanskin microflora on prepped subclavian sites for the polyurethane foammatrix described in example 3 in healthy volunteers (N=12). The methodof testing was based on that described by Maki et al 2008. The controldressing is polyurethane foam matrix with no chlorhexidine di-gluconateand no polyanhydroglucuronic acid. Bacterial counts are expressed as log10 CFU/cm². There is a statistically significant difference (P<0.001)between test and control dressings at both day 7 and day 10. Skinprepping was carried out for 1 minute with 70% isopropyl alcohol;

FIG. 5 compares mean wound surface area in a study 1 of an untreatedcontrol (dashed line (- - -) un-treated wounds), a test item (solidline—wounds treated with the test dressing device of Example 3), and acontrol dressing (dotted line ( . . . ));

FIG. 6 demonstrates the change in wound surface area of an untreatedcontrol (dashed line (- - -) un-treated wounds), a test item (solidline—wounds treated with the test dressing device of Example 3), and acontrol dressing (dotted line ( . . . ));

FIG. 7 demonstrates oedema development of an untreated control (dashedline (- - -) un-treated wounds), a test item (solid line—wounds treatedwith the test dressing device of Example 3), and a control dressing(dotted line ( . . . ));

FIGS. 8(a) to 8(h) illustrates some different physical embodiments of awound dressing device of the invention; and

FIGS. 9(a) to 9(b) shows representative micrographs of polyurethane foamA) without the impregnation of haemostatic calcium sodiumpolyanhydroglucuronic acid and B) with the impregnation of calciumsodium polyanhydroglucuronic acid. The apparatus in FIG. 9(b) indicateparticles of calcium-sodium polyanhydroglucuronic acid.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides wound dressings for controlling minor bleeding atthe access sites of IV catheters and similar percutaneous devices.Moreover the invention provides protection at the access site andcontains a broad spectrum antimicrobial agent to help resist microbialcolonization of the dressing. The device also successfully reducesbleeding time. The dressing device provides advantages over other IVsite dressings as it contains a hemostatic agent.

In one embodiment of the invention polyanhydroglucuronic acid isincorporated into the polymeric base material as the hemostatic agentand chlorhexidine di-gluconate is incorporated as the broad spectrumantimicrobial agent.

The device may have a moisture vapor permeable backing to allow formoisture transmission. The backing may, for example, comprise a thinpolyurethane film.

The system of the present invention has been shown to effectivelymaintain antimicrobial efficacy over a period of up to 7 days.

On complete saturation with an aqueous medium the absorption capacity ofthe foam of the present invention is typically greater than 8 times(wt/wt relative to the dry weight of the dressing). Preferred absorptioncapacity of the dressing is 10 to 15 times (wt/wt).

In one embodiment of the system the polymeric base material ispolyurethane foam. The components that make up the system may be presentin the system with final concentrations of, for example, 8% (w/w)polyanhydroglucuronic acid 11% (w/w) chlorhexidine di-gluconate and 81%hydrophillic flexible polyurethane foam.

The dressings of the invention will generally be sterile. Sterilizationmay be carried out using gamma irradiation but other sterilizationmethods such as ethylene oxide sterilization may also be used.

In one embodiment, the dressing device has an adhesive technology on theskin contacting surface to aid in site securement and also for removaland re-securement.

In one embodiment the wound dressing is circular with an outer diameterof 0.6 to 2 inches (1.52 to 5.08 cm). The outer diameter may be aboutone inch (2.54 cm). The dressing of the invention will typically have acentral access aperture to facilitate passage of an IV catheter line orother similar percutaneous device.

In other embodiments the central access aperture may be “x” or “T”shaped. One embodiment of the device has a circular cut central accesssite. The size of the central access site may vary from typically 1 mmto 10 mm.

In further embodiments of the invention the device may be non-circular.

Having described the invention in general terms, reference is now madeto specific non-limiting examples.

The invention provides a hemostatic and wound healing promotingantimicrobial dressing for general wound use, but also particularly forcontrolling minor bleeding at the access sites of IV catheters andsimilar percutaneous devices. Moreover the invention promotes woundhealing while providing protection at the access site by slow release ofa broad-spectrum antimicrobial agent to help resist microbialcolonization of the dressing. The device also successfully reducesbleeding time. The antimicrobial hemostatic dressing device describedherein provides significant advantages over prior art dressing forms asit provides for wound healing in combination with hemostasis andcontamination and infection control while avoiding antagonism betweenpro-healing, hemostatic and antimicrobial elements.

Example 1 Hemostatic and Antimicrobial Polyurethane Foam Preparations

To prepare hemostatic and antimicrobial foam the hemostatpolyanhydroglucuronic acid (PAGA) (HemCon Medical Technologies EuropeLtd, Dublin) and the antimi-crobial compound chlorhexidine di-gluconate(CHG) (Kapp Technologies LLC, New Jersey) were used. Polyurethane foamdressings were prepared with varying concentrations of PAGA and CHGrelative to the final dry weight of polyurethane foam. The polyurethanefoam used is type MS50P(w) Lendell medical foam available from FiltronaPorous Technologies (www.filtronaporoustechnologies.com)

Usable Width: 15 inches (381 mm) Thickness: 0.22 inches (5.6 mm) %Moisture: 2% Density: 6.0 pcf (96 Kg/m³) Tensile Strength: 51.0 psi (352kPa) Target Elongation: 194% Tear Strength: 5.6 pli (0.98 kN/m) CDF@50%:0.74 psi (5.14 kPa) Durometer: 47 shore Cell Size: 131 ppi Absorption:15 g/g Expansion 75% Wrung Retention: 1.2 g/g

The polyurethane foam was produced by firstly producing a prepolymercomprising a poly-isocyanate [OCN—R—NCO]_(n) and dial [OH—R—OH] whichwere mixed in a pre-polymer reaction vessel. The components of theprepolymer were mixed together using agitation in a mechanical mixer forover ten minutes ensuring that all components were thoroughly mixed. Thepolyurethane polymerisation reaction occurred in the pre-polymer mixingvessel. In a separate vessel the PAGA and CHG were blended together in avessel containing only water and surfactant with continual mixing untila homogenous suspension had been achieved. Unlike other hemostats thePAGA hemostat had the solubility and viscosity characteristics thatallow for aqueous mixing and it additionally demonstrates chemicalinertness towards the CHG and silver entities to allow such aqueousphase preparation. The water content of the aqueous phase ranged up to300% stoichiometric equivalents to the pre-polymer. Surfactants chosenfrom the group silicone oils, polydimethylsiloxane-polyoxyalkylene blockcopolymers, nonylphenol ethoxylates, or other similar acting organiccompounds used for the dual purpose of acting as anti-foaming compoundsin the aqueous phase while regulating the correct cell size andstructure and overall physical appearance of the foam. The aqueous phasecontaining the actives and the reacted prepolymer mix were then bothindependently pumped to a third vessel where they were physically mixedby mechanical means ensuring a homogenous mixture. The pre-polymer andaqueous phase mixture was then dispensed from the mixing vessel onto aconveyer belt coated with a carrier liner to prevent adherence to thebelt. The water of the aqueous phase reacted with the isocyanate groupsof the pre-polymer and CO₂ gas was expelled which caused the foam torise to desired height 0.375 inches. The polyurethane foam was thencovered with a nitrogen blanket to prevent further reaction and allowedto cure and dry for 24-72 hrs. A number of different formulations wereprepared for manufacturing suitability. The formulations with theimpregnated components are outlined in Table 1.

TABLE 1 Prepared foam formulations PAGA CHG Polyurethane (w/w %) (w/w %)(w/w %) 15 30 55 15 22.5 62.5 15 15 70 15 7.5 68.5 15 5 80 11.25 22.566.25 7.5 15 68.5 3.75 7.5 88.25

Example 2 Antibacterial Efficacy of Prepared Formulations Calcium SodiumSalt Polyanhydroglucuronic Acid and Chlorhexidine Di-Gluconate in aPolyurethane Foam

Polyurethane foam matrix dressings were prepared with the calcium sodiumsalt of polyanhydroglucuronic acid (15% w/w) and w/w percentages of CHGat 0%, 5%, 11%, 15%, 23% and 30% as presented in Example 1. Theseformulations were investigated for their antibacterial efficacy againstmethicillin-resistant Staphylococcus aureus (MRSA) using AATCC TestMethod 100 “Assessment of Antibacterial Finishes on Textiles”.

Analysis of FIG. 1 indicates that the acceptable minimum low range ofchlorhexidine di-gluconate percentage weight fraction in thepolyurethane foam matrix is 9% (20 mg) to 16% (35 mg) w/w since thisrange achieves the acceptable>Log 4 reduction.

The results for gamma-irradiated sterilized testing andnon-gamma-irradiated testing are presented in Table 2.

TABLE 2 Formulations of PAGA impregnated PU foam with increasing CHGconcentrations 5% 11% 15% 23% 30% CHG (w/w) (w/w) (w/w) (w/w) (w/w) LogReduction 2.3 >4.7 5.3 >5.4 >5.0 (Sterile) Log Reduction2.7 >5.2 >5.3 >5.4 5.3 (Non-sterile)

Example 3 Device Assembly

A catheter access site dressing device to control bleeding was preparedby impregnating calcium sodium salt of polyanhydroglucuronic acid intopolyurethane foam. CHG was incorporated to achieve an antimicrobialefficacy of greater than 4 log in 24 hours. A formulation as describedin Table 3 was prepared and a moisture vapor permeable backing thatcomprised of polyurethane film with a MVTR of 1000 gm/m²/24 hour (3M)was adhered.

TABLE 3 IV site device composition Formulation (% w/w) Ingredients finalformulation Chlorhexidine gluconate 11 Calcium-sodiumpolyanhydroglucuronic acid 8 Hydrophillic flexible polyurethane foam 81

The polyurethane foam matrix was die cut into 25. mm diameter disks witha central 4 mm diameter section removed from each disk. A radial slitwas also punched from the center of the disk to the outside of the disk.The slit and 4 mm punch are designed to allow catheter access. Thedressing is sterilized by gamma irradiation between 25 and 45 kGy,sufficient to produce a sterility assurance limit (SAL) of 10⁻⁶.

The device described was tested for antimicrobial efficacy against anumber of micro-organisms including gram positive and gram negativebacteria, fungi and yeast. The antimicrobial efficacy was tested usingthe AATCC Test Method 100 “Assessment of Antibacterial Finishes onTextiles”. In summary 1.0 ml of test organism suspension at a minimum of1×10⁶ CFU/ml was inoculated to the test sample. At selected time points(time zero and 24 hours) organisms were extracted in a neutralizer media(D/E broth) which was diluted and plated. Log reduction and percentreduction were determined. The results obtained are shown in Table 4.

TABLE 4 Antimicrobial results of the IV site device Decrease of CFUnumber/ Micro-organism 24 hours Staphylococcus aureus >4 logStaphylococcus epidermidis >4 log Enterococcus faecium >4 logEscherichia coli >4 log Pseudomonas aeruginosa >4 log Acinetobacterbaumanii >4 log Klebsiella pneumoniae >4 log Candida albicans >4 logAspergillus niger >4 log

Example 4 In Vitro Hemostatic Efficacy

The device described in Example 3 was tested for its ability to activatethe intrinsic blood coagulation cascade, specifically coagulation factorXIIa and kallikrein. In summary, 0.5 cm² of the device and also acontrol device which was another polyurethane IV site device but withoutpolyanhydroglucuronic acid (1″ DISK, 4.0 mm centre hole with radial slitand containing 92 mg CHG (Biopatch; Ethicon)), were placed inEppendorfs. 0.25 ml of deionized H₂O was added to the dressings andincubated at room temperature for 10 min. After 10 min incubation, thedressings were compressed and the fluid supernatant removed.Subsequently, 45 ul of the fluid supernatant was added to freshEppendorfs. Then 90 ul of deionized H₂O was added along with 45 ul ofnormal coagulation control plasma. The samples were mixed and incubatedat room temperature for 10 min. After the incubation stage 40 ul of eachsample were added to microtiter plate wells and 40 ul of 0.8 mM S-2302(specific Factor XIIa and kallikrein chromogenic substrate) was thenadded to initiate the reaction. The reaction was allowed to proceed for3 minutes and then the optical density at 405 nm was read. The resultsfor this study are presented in Table 5.

TABLE 5 Activation of Factor XIIa and kallikrein Mean Optical Density @405 nm Activity Sample (3 min read) Rate/min PAGA containing 53.40 17.80PU Foam IV device Other non PAGA 0 0 containing PU Foam IV device

The control IV site dressing not containing PAGA did not activate thecoagulation factor XIIa and kallikrein of the intrinsic coagulationsystem. The device described by Example 3 did activate the intrinsiccoagulation enzymes. Such activation is consistent with oxidizedcellulose mechanism of action and this demonstrated the potential of thedevice to be a hemostat.

Example 5 Hemostatic Efficacy—In Vivo Measurements

Having established the potential for hemostatic activity in Example 4the device was tested for hemostatic activity in a suitable in vivobleeding model. Devices of the formulation as described in Example 3were tested for their hemostatic efficacy in vivo in a rabbit ear model.

The study was divided in two periods. Within the first test period (D+1)the Test Item was tested on the left ear of the rabbit, the right earwas used as control. Within the second period (D+3) the Test Item wastested on the right ear of the rabbit, the left ear was used as acontrol. Bleeding was caused by puncture of a lateral ear vein with aninjection needle (external diameter always 0.9 mm). On D+1 the puncturewas performed at an acral part of the ear, on D+3 the puncture wasperformed cranially. Distance between both punctures was 2-3 cm. Thetest and control were applied immediately after the puncture wounds weremade. Test items and controls were weighed before their use andimmediately after cessation of bleeding. Also the time from start to theend of bleeding was measured.

In this study wounds treated with the Test Item bled for a shorterperiod of time and had a smaller blood loss compared to the control(Pur-Zellin® cellulose swab, HARTMANN-RICO a.s.) thereby demonstratingthe hemostatic efficacy of the device. Data demonstrating the in vivohemostatic efficacy of the device is outlined in Table 7.

TABLE 11 Results for the device in time to stop bleeding and blood lossmass Test Item (n = 16) Control (n = 16) Average quantity of 0.167 ±0.18 1.311 ± 1.08  Absorbed Blood (g) Average Time of Bleeding  48.8 ±20.1 89.4 ± 77.4 (seconds)

Example 6 Wound Healing

The effect on wound healing of the device prepared with the compositionof Example 3 was assessed on dermal wound healing in two separate invivo studies on rats.

Dressings prepared with the composition of Example 3 were assessed invivo for their effect on dermal wound healing in rats. Each of twelveanimals received three dorsal full thickness wounds created with an 8 mmdermal punch. Following wound creation the wound was covered with a testsample, a control dressing (non PAGA containing IV site dressing as inExample 4) or left untreated. The wound sites on each animal werecovered with a secondary dressing. Animals were observed daily to ensureintegrity of the wound, to observe signs of general clinical health andto record wound measurements. The same dressing that was removed wasreplaced on the wound after each measurement had been taken. Dressingswere changed as necessary depending on the degree of saturation withexudate and wear time was limited to a maximum of 7 days exposure of asingle treatment on the wound.

All wounds healed comparably by day 14 with the test article of thecomposition of Example 3 performing between the untreated wound (seeFIG. 5) and the control dressing. However, it could be seen that duringthe mid-stage of the study the animals from the control dressing groupshowed slower dermal healing compared to the described device and thenegative control. This can be attributed to the significantly higher CHGcontent (92 mg/dressing or 30% (w/w)) of the control dressing.

Example 7 Further Wound Healing and Oedema Formation

Dressings prepared with the composition of Example 3 were assessed invivo for their effect on dermal wound healing in rats in an experimentsimilar to that described in Example 6. Each of ten animals receivedthree dorsal full thickness wounds to the depth of the subcutis createdwith a 10 mm dermal punch. Following wound creation each of the threewound on each animal was covered with either a test sample, a controldressing (non PAGA containing IV site dressing as in Example 4 and 6) orleft untreated. The wound sites on each animal were covered with asecondary dressing. Animals were observed daily to ensure integrity ofthe wound, to observe signs of general clinical health and to recordwound measurements. The same dressing that was removed was replaced onthe wound after each measurement had been taken. Dressings were changedas necessary depending on the degree of saturation with exudate and weartime was limited to a maximum of 7 days exposure of a single treatmenton the wound. The wounds were also evaluated for signs of erythema andoedema.

As with the study described in FIGS. 9(a) and 9(b) all wounds healedcomparably by day 10 with the test article of the composition of Example3 performing between the untreated wound and control dressing (See FIG.6). There were no visible signs of erythema development at any of thewound sites (Table 12). Slight oedema formation was reported foruntreated wounds and those treated with the test item (FIG. 7 and Table13). In general a similar response was observed for un-treated woundsand wounds treated with the test item. Oedema formation was morepronounced in wounds treated with the control dressing which contained asignificantly higher fraction of CHG (30% w/w).

Generally, untreated wounds and wounds treated with the test item healedin similar manners. Both healed at a faster rate than wounds treatedwith control dressing and the higher CHG concentration. Also Oedemaformation was less pronounced in these wounds compared to wounds treatedwith control dressing. The less favorable wound healing results seen forthe control dressing can be attributed to the higher CHG content (30%w/w).

TABLE 12 Erythema Formation Erythema Average Score Day 0 1 2 3 4 5 6 7 89 10 Un-treated 1 0 0 0 0 0 0 0 0 0 0 Test Item 1 0 0 0 0 0 0 0 0 0 0Control Dressing 1 0 0 0 0 0 0 0 0 0 0 Key: (0 = Normal (no erythema), 1= Slight erythema, 2 = Mild erythema, 3 = Severe erythema)

TABLE 13 Oedema Development Oedema Average Score Day 0 1 2 3 4 5 6 7 8 910 Un-treated 1 1 1.3 1.2 1.1 1.1 1.1 1.1 1.1 1.1 1 Test Item 1 1 1.11.7 1.3 1.3 1.3 1.1 1.1 1.1 1.1 Control Dressing 1.1 1 1.3 2 1.8 2 2 1.81.9 1.8 1.9 Key: (0 = Normal (No oedema), 1 = Slight oedema, 2 = Mildoedema, 3 = Severe oedema)

Example 8 Sustained Antimicrobial Efficacy-Log Reduction

To demonstrate the sustained antimicrobial efficacy of was dressingformulation in example 3 over 24 hours and 7 days, AATCC Test Method100-2004 “Assessment of Antimicrobial Finishes on Textiles” was used.The results of this testing (Table 14) demonstrate that the formulationin example 3 is highly effective in controlling a broad range of gramnegative and gram positive bacteria as well as the fungi C. albicans andA. niger. Also a modified version of the AATCC Test Method 100 wasinvestigated. In the modified AATCC 100 test method, in addition totesting dressing samples following 24 hour exposure to the testorganisms, reference and test dressings are also exposed for 6 days to amock wound environment that potentially could lead to loss ordegradation of the antimicrobial activity. Following the 6-day exposure,the dressings are inoculated and the test conducted according to thestandard AATCC Test Method 100. Dressing were tested against a number ofmicro-organisms including gram positive and gram negative bacteria anddimorphic fungi/yeast. The log reduction data observed following 24hours and 7 days is outlined in Table 15 below. A log reduction ofgreater than 4 log was recorded for each of the test organismsdemonstrating the sustained antimicrobial activity of the antimicrobialagent in the dressing.

TABLE 14 Standard AATCC antimicrobial finish testing 24 hrs Log 7 daysLog Micro-organism Reduction Reduction Staphylococcus aureus CCM 71105.50 6.31 Staphylococcus epidermidis CCM 7221 5.53 6.18 Enterococcusfaecium CNCTC 5773 5.52 5.51 Escherichia coli CCM 4517 5.58 6.38Pseudomonas aeruginosa CCM 1961 5.76 6.70 Acinetobacter baumanii CNCTC6168 5.55 6.16 Klebsiella pneumoniae CCM 4415 4.83 6.62 Candida albicansCCM 8215 4.72 4.71 Aspergillus niger 4.20 4.19

TABLE 15 Modified AATCC antimicrobial finish testing 7 days LogMicro-organism Reduction Staphylococcus aureus CCM 7110 >4Staphylococcus epidermidis CCM 7221 >4 Enterococcus faecium CNCTC5773 >4 Escherichia coli CCM 4517 >4 Pseudomonas aeruginosa CCM 1961 >4Acinetobacter baumanii CNCTC 6168 >4 Klebsiella pneumoniae CCM 4415 >4Candida albicans CCM 8215 >4 Aspergillus niger >4

Example 9 Sustained Antimicrobial Efficacy—Zone of Inhibition

A Kirby-Bauer Zone of Inhibition method was used to investigate thesustained antimicrobial efficacy of the dressing in Example 3 over 24hours and 7 days. Overnight cultures were prepared to a minimum inoculumcount of 1×107 CFU/ml and spread on freshly prepared agar plates. Anindividual test article was placed onto the agar plate and incubated for24 hrs at 35-37° C. The area under the test article was swabbed and theswab was transferred onto sterile agar plates. The test article was thenplaced on a freshly inoculated agar plate and the procedure repeated.The test articles were transferred each day for up to seven days. Growthfrom the swabs taken from the test articles indicated bacteriostaticaction of the antimicrobial agent while no growth indicated bactericidalaction. Samples were tested in triplicate. The bactericidal orbacteriostatic action of the dressing at 7 days is shown in Table 16.FIG. 2 shows zone of inhibition results at 24 hours while FIGS. 3A & 3Bshow the zone of inhibition % changes at 1, 2, 3, 4, 5, 6 & 7 days.

TABLE 16 Bacteriocidal or Bacteriostatic action of the deviceBacteriocidal or Micro-organism Bacteriostatic Staphylococcus aureus CCM7110 Bacteriocidal Staphylococcus epidermidis CCM 7221 BacteriocidalEnterococcus faecium CNCTC 5773 Bacteriocidal Escherichia coli CCM 4517Bacteriocidal Pseudomonas aeruginosa CCM 1961 BacteriostaticAcinetobacter baumanii CNCTC 6168 Bacteriostatic Klebsiella pneumoniaeCCM 4415 Bacteriocidal Candida albicans CCM 8215 Bacteriostatic

Example 10 A Prospective Human Clinical Study of Suppression of SkinMicroflora

The primary objective of this study was to investigate the ability ofthe polyurethane foam matrix dressing formulation of example 3 tosuppress the regrowth of skin microflora following skin preparations onhealthy human volunteers. This study was performed on healthy humanvolunteers following the method of Maki et al. 2008. The study wasindependently conducted by the Center for Laboratory Activities inPublic Health Protection and Promotion, National Reference Laboratoryfor Disinfection and Sterilization, National Institute of Health,Prague, Czech Republic.

Subjects—A group of 12 study subjects was selected and enrolled fortesting through informed consent. All were Caucasian with an average ageof 52.5 years and an age range between 25 years and 69 years. This studywas conducted to assess the capacity of the test dressings (example 3formulation) to suppress skin flora re-growth following skin preppingfor 1 minute with 70% isopropyl alcohol when compared to an inactivecontrol dressing. Each subject served as his or her own control by using8 randomized sites in the subclavian area of each volunteer. On studyday 0, baseline skin flora counts were established from randomizedsites. Skin flora count from these randomized sites was also measuredfollowing air drying immediately post-prep with 70% isopropyl alcohol.Once the remaining sites had air-dried immediately post-prep, the testdressings (example 3 formulation) and the control dressings(polyurethane foam with no CHG or oxidized cellulose) were applied tothe remaining prepped sites of the subjects. Dressings were applied tothe subclavian sites using sterile tweezers and attached by latex-free,hypoallergenic and transparent polyurethane securement dressings. Thedressings were left up to 10 days, and skin flora counts were taken at 7and 10 day time points. Skin flora was measured using standard scrubbingtechniques and the skin flora beneath the dressing quantitated throughuse of a recovery solution that was then cultured on agar plates.Wilcoxon paired tests were used for statistical testing of the level ofsignificance (P-values<0.05 were considered significant).

Disinfection of the skin prior to catheter insertion providessubstantial protection to a site, but viable bacteria may still remainon the skin and re-grow over time, thus leading to a greater possibilityof infection. Any catheter related bloodstream infection preventivestrategy should be able to reduce skin microbial colonization for theduration of the catheter insertion. The results seen in FIG. 4 show theeffect of the 70% isopropyl alcohol skin prep. The raw skin flora countswere dramatically reduced, as would be expected. It can also be observedthat after both the 7 day and 10 day time points, the test dressingsmaintained the skin flora at levels equivalent to those of the post-preplevel, whereas with the control dressings significant skin florare-growth was evident. Bacterial counts were converted to log 10 CFU/cm2prior to statistical analysis. At day 7, the test dressings showedsignificantly lower skin flora counts post-prep compared to the controldressings which had substantial re-growth (P<0.001). At day 10, testdressings also showed significantly lower re-growth (P<0.001). As can beseen (FIG. 4), the test dressing maintained the skin flora count at lessthan the post-prep count for the complete duration of the study out to10 days.

No adverse events, such as skin irritation, edema or erythema formationwere reported for the study with the test dressing. The test dressingsuccessfully and significantly prevented the re-growth of microorganismsfor up to 10 days as demonstrated by this study. After both 7 and 10days, the microbial count was seen to be less than that of the post-prepmicrobial count. As such, it would be expected that the test dressingformulation (example 3) would be an effective component of a strategy toreduce skin microbial colonization. From literature, such a reduction inskin colonization markedly reduces the risk of catheter relatedbloodstream infection [Bjornson et al. 1982, Safdar et al. 2004, Maki etal. 1997].

Example 11 Different Physical Embodiments

The produced PAGA and CHG impregnated foam described in Example 3 wasalso die cut into different sized and shaped devices. Radial slits werealways punched from the centre of the disk to the outside of the devicebut different catheter access site holes and shapes were produced. Someof these different physical embodiments of the device can be seen inFIGS. 8(a) to 8(h).

In FIG. 8(a) the device has a diameter of 1 inch (2.54 cm) with a 1.5 mmcentral access site hole and a radial slit extending outwardly from thecentral hole.

The device of FIG. 8(b) is similar to 8(a) but in this case there is a 4mm central hole.

The device of FIG. 8(c) is also similar to 8(a) but in this case thereis a 7 mm central hole.

The device of FIG. 8(d) is similar to 8(a) but in this case there is aT-shaped central access site.

The device of FIG. 8(e) has a +shaped access site whilst the device ofFIG. 8(f) has an X shaped access site.

The device of FIG. 8(g) is an orthogonal shaped device with a centralaccess site hole which may be about 4 mm and there is a radial slit.

FIG. 8(h) shows a rectangular shaped device with a central access sitehole which may be about 4 mm and again in this case there is a radialslit.

Example 12 Microscopy Analysis of Foam Constructs

The PAGA and CHG impregnated foam dressings were also studied usingmicroscopy to so demonstrate the impregnation of the dressing with PAGA.Thin sections of the dressing were cut with a scalpel and placed intowells of 6-well plates. 1 ml aliquots of a solution of 0.001% aqueousbromophenol blue were added to the well and allowed to stain at roomtemperature (RT) for 30 min. As a Negative Control, a thin section ofnon-impregnated foam dressing which did not contain PAGA, were similarlytreated, Bromophenol blue is an acid phthalein dye, commonly used as apH indicator and was used here for better visualization contrast of thepolyurethane and PAGA due to their different pHs.

After staining for 30 min, the bromophenol blue was removed and thesections of the dressings were washed with 3 ml deionized H₂O. Thewashing was repeated three times. Images of the dressings were takenusing an Olympus CKX41 microscope with an Olympus E-600 digital cameraattached at a magnification of 10×. Representative images are presentedin FIGS. 9(a) and 9(b). FIG. 9(a) shows the standard foam without activeimpregnation. The stained micrograph shows the cell structure of theindividual cell units. FIG. 9(b) shows the PAGA impregnated foam. Thestained PAGA particles can be seen in the micrograph along with thepolyurethane foam stained cells.

Although the disclosure hereof is detailed and exact to enable thoseskilled in the art to practice the invention, the physical embodimentsherein disclosed merely exemplify the invention that may be embodied inother ways. While the preferred embodiment has been described thedetails may be changed without departing from the invention.

Modifications and additions can be made to the embodiments of theinvention described herein without departing from the scope of theinvention. For example, while the embodiments described herein refer toparticular features, the invention includes embodiments having differentcombinations of features. The invention also includes embodiments thatdo not include all of the specific features described.

REFERENCES

-   Mital A, Fried L F and Piraino B, 2004 “Bleeding complications    associated with peritoneal dialysis catheter insertion” Peritoneal    Dialysis Int. 24 pp. 478-480-   Doerfler M E, Kaufman B and Goldenberg A S, 1996 “Central venous    catheter placement in patients with disorders of hemostasis” Chest    110 (1) pp. 185-188-   Bouza E, Burillo A and Munoz, 2002 “Catheter-related infections:    diagnosis and intravascular treatment” Clin. Microbial. Infect. 8:    265-274-   Maki D G, Mermel L A 1998 “Infections due to infusion therapy” Taken    from: Bennett J V, Brachman P S, eds. Hospital Infections.    Philadelphia, Pa.: Lippincott-Raven; pp. 689-724-   Raad I I, Hanna H A and Darouiche R O 2001 “Diagnosis of    Catheter—Related Bloodstream Infections: Is it necessary to culture    the subcutaneous catheter segment?” Eur. J. Clin. Microbial. Infect.    Dis. 20 pp. 566-568-   Sherertz R J, Heard S O and Raad I I, 1997 “Diagnosis of    triple-lumen catheter infection: Comparison of roll plate,    sonication and flushing methodologies” J. Clin. Microbial. 35 pp.    641-646-   Timsit J F, 2007 “Diagnosis and prevention of catheter-related    infections” Curr. Opin. Crit. Care 13 (5) pp. 563-571-   Lee R I and White P D “A Clinical Study of the Coagulation Time of    Blood” J. Am. Med. Sci., April 1913 Vol. 245 (4), 495-503-   Maki et al. “Novel Integrated Chlorhexidine-impregnated Transparent    Dressing for Prevention of Vascular Catheter-related Bloodstream    Infection: A Prospective Comparative Study in Healthy Volunteers”,    Poster Presentation at the Society for HealthCare Epidemiology of    America Conference 2008, Orlando, Fla.-   Bjornson, H. S., et al. 1982 “Association between microorganism    growth at the catheter insertion site and colonization of the    catheter in patients receiving total parenteral nutrition” Surgery,    92(4): pp. 720-727-   Safdar, N. and D. G. Maki 2004 “The pathogenesis of catheter-related    bloodstream infection with noncuffed short-term central venous    catheters” Intensive Care Med, 30(1): pp. 62-67-   Maki, D. G., et al. 1997 “Prevention of central venous    catheter-related bloodstream infection by use of an    antiseptic-impregnated catheter. A randomized, controlled trial” Ann    Intern Med, 127(4): pp. 257-266

What is claimed is:
 1. A method of protecting an insertion sitepermitting passage of a transcutaneous medical device into a patient,the method comprising: grasping a dressing device, the dressing devicecomprising: a moisture vapor permeable backing; a polyurethane foammatrix adhered to a first side of the moisture vapor permeable backing,the polyurethane foam matrix comprising: a polyanhydroglucuronic acid orsalt thereof in an amount to achieve a haemostatic effect; andchlorhexidine di-gluconate in an amount of 9% to 16% (w/w) to achieve anantimicrobial effect without adversely affecting wound healing; and anadhesive covering a second side of the moisture vapor permeable backingopposite of the first side; positioning the dressing device over theinsertion site with the second side facing toward the patient; andadhering the dressing device to the patient over the insertion site. 2.The method according to claim 1, wherein the dressing device includes acentral aperture and a slit extending from the central aperture throughan outer edge, the method further comprising positioning the centralaperature around the transcutaneous medical device.
 3. The methodaccording to claim 2, wherein the central aperture is a circular holeranging in diameter from 0.1 mm to 10 mm.
 4. The method according toclaim 2, wherein the central aperture is “x” shaped or “T” shaped. 5.The method according to claim 1, wherein the polyanhydroglucuronic acidor salt is a salt in an amount from 3% to 20% (w/w).
 6. The methodaccording to claim 1, wherein the polyanhydroglucuronic acid or salt isa salt in an amount of approximately 8% (w/w).
 7. The method accordingto claim 6, wherein the chlorhexidine di-gluconate is in an amount ofapproximately 11% (w/w).
 8. The method according to claim 6, wherein theremaining 81% (w/w) comprises the polyurethane foam matrix, wherein thepolyurethane foam matrix exhibits flexibility and hydrophilicity.
 9. Themethod according to claim 1, wherein the polyanhydroglucuronic acid orsalt thereof and the chlorhexidine di-gluconate are homogenouslydispersed through the polyurethane foam matrix.